Phenylcyano ureas have been prepared heretofore by reacting a phenyl isocyanate with cyanamide. The general procedure is described by F. Kurzer, et al Org. Syn., Coll. Vol. IV, page 213. This procedure is also referred to at column 5, lines 33-41 of U.S. Pat. No. 4,098,788 and is exemplified at column 6, lines 5-30 of that patent. As discussed in U.S. Pat. No. 4,098,788, the 1-phenyl-3-cyanoureas are used in synthesizing certain quinazolines useful in treating hypertension.
Unfortunately, the phenyl isocyanates referred to above may, and frequently are, difficult to obtain. This problem is discussed in U.S. Pat. No. 4,084,056 at column 1, lines 40-52. As an alternate to phenyl isocyanates, U.S. Pat. No. 4,084,056 indicates that the corresponding benzamides can be treated with alkali metal hypochlorite to produce amines via the Hofmann reaction. However, rather than allowing the Hofmann reaction to go to completion, at an intermediate stage certain reactive intermediates (e.g., phenyl isocyanates of N-chlorobenzamide) are "trapped" by reaction with phenols to produce the desired carbamate esters. Use of N-chloro amides is a well known variant of the Hofmann reaction. For example, Elliott, J. Chem. Soc. 121, 202-9 (1922) prepared N-chlorobenzamide and reacted this with various nucleophiles to produce phenyl carbamates and ureas. Phenylcarbamate esters have also been prepared from benzamide using molecular halogen in alcohols in the presence of alkoxides or dry alkali carbonates. See Wallis et al, Organic Reactions, Vol. III, pages 267-306. These methods involve the use of molecular halogen and/or isolation of the free N-chlorobenzamide.
In summary, methods are known to modify the Hofmann reaction so as to "trap" the intermediate isocyanate with nucleophiles in the absence or presence of water and in ways which are generally practical. However, we are not aware of any instance where cyanamide or any derivative thereof has been used as the nucleophile.
Moreover, cyanamide is known to react with halogens and hypohalites to give unidentified, unstable and even explosive products. See Beilstein E II 3, page 64. While we have encountered no problems in the use of cyanamide, and this is unexpected, customary industrial precautions should be exercised in employing the invention.